30 Day Outcomes from the SOURCE XT TAVI Post Approval Study Olaf Wendler MD PhD FRCS Professor of Cardiac Surgery King's College Hospital/King’s Health Partners, London, UK on behalf of the SOURCE XT Investigators

   Potential conflicts of interest Speaker’s name: Olaf Wendler  I have the following potential conflicts of interest to report:  Research contracts Edwards Lifesciences  Consulting Medtronic, JenaValve, Edwards Lifesciences, SJM  Employment in industry  Stockholder of a healthcare company  Owner of a healthcare company  Other(s)  I do not have any potential conflict of interest   

Introduction First TAVI performed by Alain Cribier in 2002 CE-Mark approval of the Edwards SAPIEN™ THV in 2007 The „SOURCE“ Post Approval Registry included 2300+ patients treated using the SAPIEN™ THV Data generated provided important information for new product and clinical development Next generation SAPIEN XT™ THV and its delivery systems are assessed in the „SOURCE XT“ Post Approval Study

Edwards SAPIEN XTTM Evolution Stainless Steel Frame Equine Pericardial Tissue Stainless Steel Frame Bovine Pericardial Tissue Cobalt-Chromium Frame Bovine Pericardial Tissue Semi-closed leaflets Reduced crimped profile 2004 2007 2010 Cribier-Edwards™ THV 23mm Edwards SAPIEN™ THV 23 mm and 26 mm Edwards SAPIEN XT ™ THV 23 mm, 26 mm, and 29mm 4

SOURCE - SOURCE XT Multicenter, prospective, observational, post-approval studies to Observe use of the SAPIEN/SAPIEN XT™ THV in the real world Evaluate long-term safety of SAPIEN/SAPIEN XT™ THV SOURCE was further aimed to Develope physician training Optimize patient screening and selection SOURCE XT is further aimed to Incorporate VARC definitions Include assessment of frailty Develop a TAVI risk prediction model

Design and Execution SOURCE Registry SOURCE XT Post Approval Study Patients 2307 2706 Enrollment Nov 2007 – Dec 2009 July 2010 – Oct 2011 Centers 37 94 Countries 14 17 Access Routes TF, TA TF, TA, TAO, SC THV SAPIEN™ 23mm, 26mm SAPIEN XT™ 23mm, 26mm, 29mm Adverse Event Adjudication Principal Investigators Independent Clinical Endpoint Committee, VARC Guidelines Monitored No Yes Follow-up 30 Days, annually to 2 Years 30 Days, annually to 5 Years

Executive Committee Prof. Dr. Helmut Baumgartner - Muenster, Germany Prof. Dr. Gino Gerosa - Padua, Italy Dr. Paolo Rubino - Mercogliano, Italy Prof. Dr. Patrick Nataf - Paris, France Dr. Martyn Thomas - London, United Kingdom Prof. Dr. Alec Vahanian - Paris, France Prof. Dr. Thomas Walther - Bad Nauheim, Germany Prof. Dr. Olaf Wendler-London - United Kingdom Prof. Dr. Stephan Windecker-Bern, Switzerland

Access Routes Subclavian 0.3%

Methods Focus on quality of data Centers participating had to submit consecutive group of their patient experience using the Edwards SAPIEN XT™ Decision of access route made by the individual center Cardiologists and Cardiac Surgeons as PI‘s in participating centers to support the „Heart Team“ approach „We present the interim analysis of the 30 day outcomes with a focus on TF and TA access routes“

Baseline Characteristics - Cardiac Transfemoral N = 1694 Transapical N = 906 P NYHA III/IV (%) 77.2 75.9 0.5 LV Ejection Fraction (mean ±SD) 55.3 ±17.0 53.5 ± 12.4 <.0001 Coronary Artery Disease (%) 40.2 51.8 Previous MI (%) 12.2 20.9 Previous PCI (%) 27.2 36.7 Previous CABG (%) 12.3 24.4 Atrial Fibrillation (%) 22.8 29.9 Previous Pacemaker (%) 10.0 12.7 0.03 Previous Ao Bioprosthesis (%) 1.8 4.0 0.001

Baseline Characteristics Transfemoral N = 1694 Transapical N = 906 P Age (years, mean ±SD) 81.9 ±6.6 80.2 ±6.4 <.0001 Female (%) 64.5 45.6 Previous Stroke (%) 7.3 10.6 0.005 Renal Failure (%) 24.9 35.2 Peripheral Vascular Disease (%) 14.6 33.0 Diabetes Mellitus (%) 26.8 33.7 0.0003 Porcelain Aorta (%) 4.4 10.7 Frail condition (mean±SD) 5.2 ±1.4 0.7 COPD (%) 19.6 21.9 0.2 Logistic EuroSCORE (mean±SD) 19.9 ±12.0 21.8 ±13.8 0.0004 STS Score (mean±SD) 8.4 ±7.0 8.7 ±7.2 Logistic EuroSCORE TF TA ≤40 92.3 88.5 >40 6.7 10.8 Missing 0.9 0.8

Procedural Information Characteristic Transfemoral N = 1694 Transapical N = 906 P Total Procedure Time (min, mean ±SD) 79.7 ±51.7 90.7 ±56.3 <0.0001 Fluoroscopy Time (min, mean ±SD) 15.0 ±20.8 7.4 ±19.3 Contrast Volume (ml, mean ±SD) 141.1 ±104.0 95.0 ±81.8 General Anesthesia (%) 50.1 96.0 Pre-implant BAV (%) 98.5 93.4 Annular Diameter (mm, mean ± SD) 21.7 ± 3.5 22.5 ± 3.4 Valve size implanted 23 mm (%) 26 mm (%) 29 mm (%) NA (%) 47.8 51.8 -- 0.3 33.0 41.8 23.8 1.4

Procedural Complications Adverse Events Transfemoral N = 1694 Transapical N = 906 P Conversion to Surgery (%) 0.3 0.6 Cardiac Tamponade (%) 0.7 0.1 0.04 Annular Dissection (%) 0.4 Coronary Occlusion (%) 1.0 SAPIEN-in-SAPIEN (Bailout) (%) 0.8 1.7 0.07 Valve Embolization (%) 0.9 0.2 Aborted Procedure (%) 1.1 Unable to Cross Native Valve (%) --

Clinical Outcomes at 30 Days Transfemoral N = 1694 Transapical N = 906 All-cause Mortality (%)* 4.3 9.9 Any Stroke (%)* 2.3 2.1 TIA (%) 0.6 0.7 Myocardial Infarction (%) 0.5 New Pacemaker (%) 8.0 10.9 Vascular Complication – Major (%)* 7.3 3.6 Renal Failure with Temporary Dialysis) (%) 1.2 4.0 Major Bleeding (%) 5.0 11.4 * VARC definitions /CEC Adjudicated

Subanalyses Mortality Stratified LES Transfemoral N = 1694 Transapical N=906 ≤40 4.0 8.4 >40 7.0 22.4 SAPIEN XTTM Size Transfemoral N = 1694 Transapical N=906 23mm (%) 4.3 8.9 26mm (%) 4.1 11.9 29mm (%) N/A 6.0 Missing (%) 0.6 0.06

Echo at 30 Days*: TF – TA Mean Gradient (mm Hg) EF (%) AVA(cm2) p <.0001 EF (%) p <.0001 Baseline 30 Days *Site reported, Paired observation analysis

Paravalvular Leak at 30 Days*: TF - TA *Site reported

Conclusions (I) Mortality in TF (4.3%) is one of the lowest ever reported for TF registries One third of patients were selected for a TA approach Mortality in TA has decreased but remains higher in the very high-risk patient group For 29 mm TA prostheses (not available for TF, no selection bias) mortality for TA is only 6% Compared to SOURCE, mean log EuroSCORE has decreased but stays within the label indication of 15 for the SAPIEN XTTM TA patients continue to present with more co-morbidities

Conclusions (II) Major vascular complications were more common after TF and bleeding more often seen after TA Procedural complications were rare and early hemodynamic function excellent using the SAPIEN XT™ LV ejection fraction was improved significantly using both access routes The number of patients with no/trace paravalvular leakage is high and it remains to be seen which effect this may has on the 1-year survival It remains to be seen which effect frailty has on 1-year survival